Lower incidence of CMV infection and acute rejections with valganciclovir prophylaxis in lung transplant recipients

BMC Infectious Diseases

Rune Andersson³  Salmir Nasic¹  Ulla Nyström⁴  Gunnar Mårtensson²  Inger Johansson³ 

[1] Research and Development Centre, Skaraborg Hospital, Skövde, Sweden;Department of Respiratory Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden

关键词: Valganciclovir;    Survival rates;    Lung transplantation;    Ganciclovir;    Cytomegalovirus;    Bronchiolitis obliterans syndrome;   

Others  :  1145315
DOI  :  10.1186/1471-2334-13-582

 received in 2012-10-17, accepted in 2013-12-02,  发布年份 2013

【 摘 要 】

Background

Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS). Finding a strategy to prevent CMV infection is an important issue.

Methods

We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed.

Results

For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival.

For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%).

Conclusions

A lower incidence of CMV infection/disease and acute rejections was observed with valganciclovir (3 months) when compared to oral ganciclovir (3 months). The long-term impact of CMV infection/disease was significant for BOS-free survival and survival.

【 授权许可】

   
2013 Johansson et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Fig. 1.

【 参考文献 】

• [1]Alexander BD, Tapson VF: Infectious complications of lung transplantation. Transpl Infect Dis 2001, 3:128-137.
• [2]Fishman AJ, Emery V, Freeman R, Pascual M, Rostaing L, Schlitt HJ, Sgarabotto D, Torre-cisneros J, Uknis ME: Cytomegalovirus in transplantation - challenging the status quo. Clin Transplant 2007, 21:149-158.
• [3]Snydman DR, Limaye AP, Potena L, Zamora MR, Weigand K: Update and review: state-of-the-art management of cytomegalovirus infection and disease following thoracic organ transplantation. Transplant Proc 2011, 43:S1-S17.
• [4]Johanssson I, Mårtensson G, Andersson R: Cytomegalovirus and long-term outcome after lung transplantation in Gothenburg, Sweden. Scand J Infect Dis 2010, 42:129-136.
• [5]Zuk DM, Humar A, Weinkauf JG, Lien DC, Nador RG, Kumar D: An international survey of cytomegalovirus management practices in lung transplantation. Transplantation 2010, 90:672-676.
• [6]Pescovitz MD, Rabkin J, Merion RM, Paya CV, Pirsch J, Freeman RB, O’Grady J, Robinson C, To Z, Wren K, Banken L, Buhles W, Brown F: Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients. Antimicrob Agents Chemother 2000, 44:2811-2815.
• [7]Christie JD, Edwards LB, Kucheryavaya AY, Benden C, Dobbels F, Kirk R, Rahmel AO, Stehlik J, Hertz MI: The registry of the international society for heart and lung transplantation: twenty-eighth adult lung and heart-lung transplant report-2011. J Heart Lung Transplant 2011, 30:1104-1122.
• [8]Estenne M, Maurer JR, Boehler A, Egan JJ, Frost A, Hertz M, Mallory GB Jr, Snell GI, Yousem S: Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant 2002, 21:297-310.
• [9]Zamora MR: Use of cytomegalovirus immune globulin and ganciclovir for the prevention of cytomegalovirus disease in lung transplantation. Transpl Infect Dis 2001, 3:49-56.
• [10]Todd JL, Palmer SM: Bronchiolitis obliterans syndrome: the final frontier for lung transplantation. Chest 2011, 140:502-508.
• [11]Snyder LD, Finlen-Copeland CA, Turbyfill WJ, Howell D, Willner DA, Palmer SM: Cytomegalovirus pneumonitis is a risk for bronchiolitis obliterans syndrome in lung transplantation. Am J Respir Crit Care Med 2010, 181:1391-1396.
• [12]Parada MT, Alba A, Sepúlveda C: Bronchiolitis obliterans syndrome development in lung transplantation patients. Transplant Proc 2010, 42:331-332.
• [13]Paraskeva M, Bailey M, Levvey BJ, Griffiths AP, Kotsimbos TC, Williams TP, Snell G, Westall G: Cytomegalovirus replication within the lung allograft is associated with bronchiolitis obliterans syndrome. Am J Transplant 2011, 11:2190-2196.
• [14]Ljungman P, Griffiths P, Paya C: Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 2002, 34:1094-1097.
• [15]Husain AN, Siddiqui MT, Holmes EW, Chandrasekhar AJ, McCabe M, Radvany R, Garrity ER Jr: Analysis of risk factors for the development of bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 1999, 159:829-833.
• [16]Monforte V, Lopez C, Santos F, Zurbano F, De La Torre M, Sole A, Gavalda J, Ussetti P, Lama R, Cifrian J, Borro JM, Pastor A, Len O, Bravo C, Roman A: A multicenter study of valganciclovir prophylaxis up to day 120 in CMV-Seropositive lung transplant recipients. Am J Transplant 2009, 9:1134-1141.
• [17]Valentine VG, Weill D, Gupta MR, Raper B, LaPlace SG, Lombard GA, Bonvillain RW, Taylor DE, Dhillon GS: Ganciclovir for cytomegalovirus: a call for indefinite prophylaxis in lung transplantation. J Heart Lung Transplant 2008, 27:875-881.
• [18]Zamora MR, Nicolls MR, Hodges TN, Marquesen J, Astor T, Grazia T, Weill D: Following universal prophylaxis with intravenous ganciclovir and cytomegalovirus immune globulin, valganciclovir is safe and effective for prevention of CMV infection following lung transplantation. Am J Transplant 2004, 4:1635-1642.
• [19]Chmiel C, Speich R, Hofer M, Michel D, Mertens T, Weder W, Boehler A: Ganciclovir/valganciclovir prophylaxis decreases cytomegalovirus-related events and bronchiolitis obliterans syndrome after lung transplantation. Clin Infect Dis 2008, 46:831-839.
• [20]Jaksch P, Zweytick B, Kerschner H, Hoda AM, Keplinger M, Lang G, Aigner C, Klepetko W: Cytomegalovirus prevention in high-risk lung transplant recipients: comparison of 3- vs 12-month valganciclovir therapy. J Heart Lung Transplant 2009, 28:670-675.
• [21]Palmer SM, Limaye AP, Banks M, Gallup D, Chapman J, Lawrence EC, Dunitz J, Milstone A, Reynolds J, Yung GL, Chan KM, Aris R, Garrity E, Valentine V, McCall J, Chow SC, Davis RD, Avery R: Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial. Ann Intern Med 2010, 152:761-769.
• [22]Finlen Copeland CA, Davis WA, Snyder LD, Banks M, Avery R, Davis RD, Palmer SM: Long-term efficacy and safety of 12 months of valganciclovir prophylaxis compared with 3 months after lung transplantation: a single-center, long-term follow-up analysis from a randomized, controlled cytomegalovirus prevention trial. J Heart Lung Transplant 2011, 30:990-996.
• [23]Limaye AP, Raghu G, Koelle DM, Ferrenberg J, Huang ML, Boeckh M: High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy. J Infect Dis 2002, 185:20-27.
• [24]Bhorade SM, Lurain NS, Jordan A, Leischner J, Villanueva J, Durazo R, Creech S, Vigneswaran WT, Garrity ER: Emergence of ganciclovir-resistant cytomegalovirus in lung transplant recipients. J Heart Lung Transplant 2002, 21:1274-1282.
• [25]Swarup R, Allenspach LL, Nemeh HW, Stagner LD, Betensley AD: Timing of basiliximab induction and development of acute rejection in lung transplant patients. J Heart Lung Transplant 2011, 30:1228-1235.
• [26]Thomas LD, Milstone AP, Miller GG, Loyd JE, Dummer JS: Long-term outcomes of cytomegalovirus infection and disease after lung or heart-lung transplantation with a delayed ganciclovir regimen. Clin Transplant 2009, 23:476-483.
• [27]Mitsani D, Nguyen MH, Kwak EJ, Silveira FP, Vadnerkar A, Pilewski J, Crespo M, Toyoda Y, Bermudez C, Clancy CJ: Cytomegalovirus disease among donor-positive/recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis. J Heart Lung Transplant 2010, 29:1014-1020.
• [28]Tamm M, Aboyoun CL, Chhajed PN, Rainer S, Malouf MA, Glanville AR: Treated cytomegalovirus pneumonia is not associated with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 2004, 170:1120-1123.